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Inhibition of tumor cell growth by monoterpenes in vitro: Evidence of a Ras-independent mechanism of action
KTH, Sweden.
KTH, Sweden.ORCID iD: 0000-0001-7158-6393
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1996 (English)In: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 7, no 4, 422-429 p.Article in journal (Refereed) Published
Abstract [en]

(+)-Limonene (d-limonene) and related monoterpenes show chemopreventive activity against rodent mammary carcinoma and inhibit the growth of cancer cells in vitro, One suggested mechanism for the anti-tumorigenic effect of (+)-limonene is inhibition of the post-translational isoprenylation of growth controlling Pas oncoproteins. We have here examined the growth inhibitory effects of (+)-limonene and other related monoterpenes on PANC-1 pancreas carcinoma cells (carrying a K-ras mutation) and on 12V-H-ras-transformed rat fibroblasts, (+)- and (-)-perillyl alcohol, 7-methyl-perillyl alcohol, (+)-limonene oxide and (+)-perillic acid methyl ester were all found to efficiently inhibit cell growth at 1 mM, whereas (+)-limonene caused an approximately 50% growth reduction at 5 mM, Whereas BZA-BB, an inhibitor of Ras farnesyl transferase, was found to induce morphological reversion of 12v-H-ras-transformed cells, (+)-perillyl alcohol and (+)-limonene did not induce reversion. Furthermore, monoterpenes did not decrease MAP kinase enzyme activity or collagenase promoter activity in PANC-1 cells, two functions known to be down-stream from Pas, We conclude that although effective in inhibiting the growth of tumor cells harboring activated res oncogenes, limonene and (+)-perillyl alcohol are unlikely to act by inhibiting Ras function.

Place, publisher, year, edition, pages
1996. Vol. 7, no 4, 422-429 p.
Keyword [en]
d-limonene, isoprenylation, map kinase, monoterpene, ras, d-limonene, exocrine pancreas, carcinogenesis, isoprenylation, proliferation, carcinoma, enzymes, genes, line
National Category
Natural Sciences Medical and Health Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-14104ISI: A1996UX71900008OAI: oai:DiVA.org:lnu-14104DiVA: diva2:440827
Note
Ux719 Times Cited:24 Cited References Count:23Available from: 2011-09-13 Created: 2011-09-13 Last updated: 2017-01-11Bibliographically approved

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